Healthy Volunteers
Conditions
Keywords
Drug therapy
Brief summary
The purpose of this study is to determine the mass balance, routes of elimination and characterize the metabolic profiles of a single intravenous dose of \[14C\]-TAK-954, identify major circulating and excreted metabolites. This study will also determine the single-dose PK of total radioactivity, TAK-954 and its metabolites where possible.
Detailed description
The drug being tested in this study is called TAK-954. This study will assess the mass balance, metabolic profiles and routes of elimination of single intravenous dose of \[14C\]-TAK-954, and will determine the major circulating and excreted metabolites and single-dose PK of total radioactivity, TAK-954, THRX513466, and THRX 913682 in healthy male participants. The study will enroll approximately 6 participants. All participants will receive a single dose of \[14C\]-TAK-954 0.5 mg on Day 1. This single-center trial will be conducted in Netherlands. The overall time to participate in this study is approximately 6 to 7 weeks. Participants will make a final visit to the clinic 15 days after last dose of study drug for a follow-up assessment.
Interventions
DRUG[14C]-TAK-954
\[14C\]-TAK-954 intravenous infusion.
Sponsors
Millennium Pharmaceuticals, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
1. Be a man aged 18 to 55 years, inclusive, at the screening visit. 2. Have a body mass index (BMI) greater than or equal to (\>=) 18 and less than or equal to (\<=) 30 kilogram per square meter (kg/m\^2) and a body weight greater than (\>) 50 kilogram (kg) at the screening visit. 3. Be a nonsmoker who has not used tobacco- or nicotine-containing products (example, nicotine patch) for at least 6 months before administration of the initial dose of trial drug. 4. Meet the following birth control requirements: * Is a male participant who is sterile or agrees to use an appropriate method of contraception, including a condom, from the first dose of study drug until 30 days after the last dose of study drug. No restrictions are required for a vasectomized male participant provided that the participant is at least 1 year postbilateral vasectomy procedure before the first dose of study drug. A male participant whose vasectomy procedure was performed less than 1 year before the first dose of study drug must follow the same restrictions as a nonvasectomized man. Appropriate documentation of surgical procedures should be provided. * Is a male participant who agrees to not donate sperm from trial drug administration on the first day of the first dose until 30 days after the last dose of study drug.
Exclusion criteria
1. Has total 14C radioactivity measured by accelerator mass spectrometry in plasma (during screening) exceeding 14C/12C ratio 1.1E-12. 2. Participated in any study with a radiation dose above 0.1 millibecquerel (MBq) or radiation burden above 0.1 millisievert (mSv) within 1 year before screening. 3. Was exposed to significant radiation (example, serial x-ray or computed tomography scans, barium meal, current employment in a job requiring radiation exposure monitoring) within 12 months before check-in. 4. Irregular defecation pattern (less than once per 2 days). 5. Has a history of alcohol consumption exceeding 2 standard drinks per day on average (1 glass is approximately equivalent to beer 354 milliliter \[mL\]/12 ounce \[oz\], wine 118 mL/4 oz, or distilled spirits 29.5 mL/1 oz). 6. Consumes excessive amounts, defined as greater than 6 servings (1 serving is approximately equivalent to 120 mg of caffeine) of coffee, tea, cola, energy drinks, or other caffeinated beverages per day. 7. Has a substance abuse disorder.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cumulative Percentage of Administered Radioactivity Recovered in Urine | Day 1 pre-dose and at multiple time points (up to 264, 312, and 336 hours) post-dose | — |
| Cumulative Percentage of Administered Radioactivity Recovered in Feces | Day 1 pre-dose and at multiple time points (up to 264, 312, and 336 hours) post-dose | — |
| Cumulative Percentage of Radioactivity in Urine and Feces Combined | Day 1 pre-dose and at multiple time points (up to 264, 312, and 336 hours) post-dose | — |
| Normalized Recovery as Percentage of Dose for TAK-954 and TAK-954 Metabolites in Urine and Feces Combined | Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose | Percentage of dose recovered for TAK-954 and its metabolites derived from 0-168 hour sampling was normalized for 100% recovery. |
| Normalized Recovery as Percentage of Dose for TAK-954 and TAK-954 Metabolites in Urine | Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose | Percentage of dose recovered for TAK-954 and its metabolites derived from 0-168 hour sampling was normalized for 100% recovery. |
| Normalized Recovery as Percentage of Dose for TAK-954 and TAK-954 Metabolites in Feces | Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose | Percentage of dose recovered for TAK-954 and its metabolites derived from 0-168 hour sampling was normalized for 100% recovery. |
| Mean Percent of Total Radioactivity in Plasma for TAK-954 and TAK-954 Metabolites | Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose | — |
| Cumulative Percentage of Dose Excreted in Urine for TAK-954 | Day 1 pre-dose and at multiple time points (up to 264, 312, and 336 hours) post-dose | — |
| Cumulative Percentage of Dose Excreted in Feces for TAK-954 | Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose | The cumulative percentage of dose excreted in feces as TAK-954 derived from 0-168 hour sampling was normalized for 100% recovery. |
| Mean Concentration of Total Radioactivity in Whole Blood and Plasma [14C]-TAK-954 | Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose | — |
| Cmax: Maximum Observed Plasma and Whole Blood Concentrations of Radioactivity for [14C]-TAK-954 | Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose | — |
| Cmax: Maximum Observed Plasma Concentration for TAK-954 and TAK-954 Metabolites | Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose | — |
| AUClast: Area Under the Plasma and Whole Blood Radioactivity-time Curve From Time 0 to the Time of the Last Quantifiable Radioactivity for [14C]-TAK-954 | Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose | — |
| AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-954 and TAK-954 Metabolites | Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose | — |
| AUC∞: Area Under the Plasma and Whole Blood Radioactivity-time Curve From Time 0 to Infinity for [14C]-TAK-954 | Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose | — |
| AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-954 and TAK-954 Metabolites | Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose | — |
| Tmax: Time to Reach the Maximum Plasma and Whole Blood Radioactivity for [14C]-TAK-954 | Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose | — |
| Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-954 and TAK-954 Metabolites | Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose | — |
| t1/2z: Terminal Disposition Phase Half-life of Radioactivity in Plasma and Whole Blood for [14C]-TAK-954 | Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose | — |
| t1/2z: Terminal Disposition Phase Half-life in Plasma for TAK-954 and TAK-954 Metabolites | Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose | — |
| CL: Total Clearance After Intravenous Administration for [14C]-TAK-954 | Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose | — |
| CL: Total Clearance of TAK-954 After Intravenous Administration of [14C]-TAK-954 | Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose | — |
| Vz: Volume of Distribution During the Terminal Disposition Phase After Intravenous Administration for [14C]-TAK-954 | Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose | — |
| Vz: Volume of Distribution During the Terminal Disposition Phase After Intravenous Administration for TAK-954 | Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose | — |
| Aet Urine: Amount of Total Radioactivity Excreted in Urine From Time 0 to Time t for [14C]-TAK-954 | Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose | — |
| Aet Urine: Amount of Drug Excreted in Urine From Time 0 to Time t for TAK-954 | Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose | — |
| Aet Feces: Amount of Total Radioactivity Excreted in Feces From Time 0 to Time t for [14C]-TAK-954 | Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose | — |
| Fet Urine: Fraction of Drug Excreted in Urine From Time 0 to Time t for TAK-954 | Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose | — |
| Fet Urine: Fraction of Total Radioactivity Excreted in Urine From Time 0 to Time t for [14C]-TAK-954 | Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose | — |
| Fet Feces: Fraction of Radioactivity Excreted in Feces From Time 0 to Time t for [14C]-TAK-954 | Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose | — |
Secondary
| Measure | Time frame |
|---|---|
| Ratio of Total Radioactivity in Whole Blood to Plasma | Day 1 pre-dose and at multiple time points (up to 264 hours) post-dose |
| Ratio of AUC∞: Ratio of Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-954 to Total Radioactivity in Plasma TAK-954 | Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose |
| Percentage of Participants Who Experience at Least One Treatment-emergent Adverse Event (TEAE) | Baseline up to Day 31 |
| Percentage of Participants With Adverse Events (AEs) Leading to Discontinuation of [14C]-TAK-954 | Baseline up to Day 15 |
Countries
Netherlands
Participant flow
Recruitment details
Participants took part in the study at 1 investigative site in the Netherlands from 30 April 2018 to 01 June 2018.
Pre-assignment details
Healthy participants were enrolled to receive a single 60-minute intravenous infusion of 0.5 milligram (mg) TAK-954 containing a microtracer of \[14C\]-TAK-954.
Participants by arm
| Arm | Count |
|---|---|
| [14C]-TAK-954 0.5 mg \[14C\]-TAK-954 0.5 mg (containing approximately 1.5 µCi) of radioactive tracer administered as a 60-minute infusion, intravenously, once on Day 1. | 6 |
| Total | 6 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | [14C]-TAK-954 0.5 mg |
|---|---|
| Age, Continuous | 39.5 years STANDARD_DEVIATION 13.98 |
| Body mass index | 24.2 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 1.72 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Height | 177.2 centimeter (cm) STANDARD_DEVIATION 7.78 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 5 Participants |
| Region of Enrollment Netherlands | 6 Participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 6 Participants |
| Weight | 76.37 kilogram (kg) STANDARD_DEVIATION 8.694 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 6 |
| other Total, other adverse events | 3 / 6 |
| serious Total, serious adverse events | 0 / 6 |
Outcome results
Primary
Aet Feces: Amount of Total Radioactivity Excreted in Feces From Time 0 to Time t for [14C]-TAK-954
Time frame: Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose
Population: The PK analysis set included all the participants of safety analysis set with sufficient concentration data to facilitate the derivation of at least 1 PK parameter from the concentration time data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| [14C]-TAK-954 0.5 mg | Aet Feces: Amount of Total Radioactivity Excreted in Feces From Time 0 to Time t for [14C]-TAK-954 | 144 mcg eq | Standard Deviation 12.9 |
Primary
Aet Urine: Amount of Drug Excreted in Urine From Time 0 to Time t for TAK-954
Time frame: Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose
Population: The PK analysis set included all the participants of safety analysis set with sufficient concentration data to facilitate the derivation of at least 1 PK parameter from the concentration time data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| [14C]-TAK-954 0.5 mg | Aet Urine: Amount of Drug Excreted in Urine From Time 0 to Time t for TAK-954 | 157 microgram (mcg) | Standard Deviation 16.4 |
Primary
Aet Urine: Amount of Total Radioactivity Excreted in Urine From Time 0 to Time t for [14C]-TAK-954
Time frame: Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose
Population: The PK analysis set included all the participants of safety analysis set with sufficient concentration data to facilitate the derivation of at least 1 PK parameter from the concentration time data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| [14C]-TAK-954 0.5 mg | Aet Urine: Amount of Total Radioactivity Excreted in Urine From Time 0 to Time t for [14C]-TAK-954 | 278 microgram equivalent (mcg eq) | Standard Deviation 16.2 |
Primary
AUC∞: Area Under the Plasma and Whole Blood Radioactivity-time Curve From Time 0 to Infinity for [14C]-TAK-954
Time frame: Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose
Population: The PK analysis set included all the participants of safety analysis set with sufficient concentration data to facilitate the derivation of at least 1 PK parameter from the concentration time data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| [14C]-TAK-954 0.5 mg | AUC∞: Area Under the Plasma and Whole Blood Radioactivity-time Curve From Time 0 to Infinity for [14C]-TAK-954 | Plasma | 87.2 h*ng eq/mL |
| [14C]-TAK-954 0.5 mg | AUC∞: Area Under the Plasma and Whole Blood Radioactivity-time Curve From Time 0 to Infinity for [14C]-TAK-954 | Whole Blood | 79.0 h*ng eq/mL |
Primary
AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-954 and TAK-954 Metabolites
Time frame: Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose
Population: The PK analysis set. PK data for metabolites could not be evaluated since metabolites were \< lower limit of quantification and apparent terminal elimination portion of the concentration-time curve could not be characterized.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| [14C]-TAK-954 0.5 mg | AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-954 and TAK-954 Metabolites | 55.7 h*ng/mL |
Primary
AUClast: Area Under the Plasma and Whole Blood Radioactivity-time Curve From Time 0 to the Time of the Last Quantifiable Radioactivity for [14C]-TAK-954
Time frame: Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose
Population: The PK analysis set included all the participants of safety analysis set with sufficient concentration data to facilitate the derivation of at least 1 PK parameter from the concentration time data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| [14C]-TAK-954 0.5 mg | AUClast: Area Under the Plasma and Whole Blood Radioactivity-time Curve From Time 0 to the Time of the Last Quantifiable Radioactivity for [14C]-TAK-954 | Plasma | 83.6 h*ng eq/mL |
| [14C]-TAK-954 0.5 mg | AUClast: Area Under the Plasma and Whole Blood Radioactivity-time Curve From Time 0 to the Time of the Last Quantifiable Radioactivity for [14C]-TAK-954 | Whole Blood | 75.4 h*ng eq/mL |
Primary
AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-954 and TAK-954 Metabolites
Time frame: Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose
Population: The PK analysis set included all the participants of safety analysis set with sufficient concentration data to facilitate the derivation of at least 1 PK parameter from the concentration time data. PK data for TAK-954 metabolite THRX913682 could not be evaluated since its plasma levels were \< lower limit of quantification.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| [14C]-TAK-954 0.5 mg | AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-954 and TAK-954 Metabolites | TAK-954 | 55.4 hour*nanogram per milliliter (h*ng/mL) |
| [14C]-TAK-954 0.5 mg | AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-954 and TAK-954 Metabolites | THRX-513466 | 0.0371 hour*nanogram per milliliter (h*ng/mL) |
Primary
CL: Total Clearance After Intravenous Administration for [14C]-TAK-954
Time frame: Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose
Population: No participant was analyzed since this outcome measure was not planned to be assessed but added in the protocol summary by error.
Primary
CL: Total Clearance of TAK-954 After Intravenous Administration of [14C]-TAK-954
Time frame: Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose
Population: The PK analysis set included all the participants of safety analysis set with sufficient concentration data to facilitate the derivation of at least 1 PK parameter from the concentration time data.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| [14C]-TAK-954 0.5 mg | CL: Total Clearance of TAK-954 After Intravenous Administration of [14C]-TAK-954 | 8.97 L/h |
Primary
Cmax: Maximum Observed Plasma and Whole Blood Concentrations of Radioactivity for [14C]-TAK-954
Time frame: Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose
Population: The PK analysis set included all the participants of safety analysis set with sufficient concentration data to facilitate the derivation of at least 1 PK parameter from the concentration time data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| [14C]-TAK-954 0.5 mg | Cmax: Maximum Observed Plasma and Whole Blood Concentrations of Radioactivity for [14C]-TAK-954 | Plasma | 6.28 ng eq/mL |
| [14C]-TAK-954 0.5 mg | Cmax: Maximum Observed Plasma and Whole Blood Concentrations of Radioactivity for [14C]-TAK-954 | Whole Blood | 5.78 ng eq/mL |
Primary
Cmax: Maximum Observed Plasma Concentration for TAK-954 and TAK-954 Metabolites
Time frame: Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose
Population: The PK analysis set included all the participants of safety analysis set with sufficient concentration data to facilitate the derivation of at least 1 PK parameter from the concentration time data. PK data for TAK-954 metabolite THRX913682 could not be evaluated since its plasma levels were less than (\<) lower limit of quantification.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| [14C]-TAK-954 0.5 mg | Cmax: Maximum Observed Plasma Concentration for TAK-954 and TAK-954 Metabolites | TAK-954 | 5.91 nanogram per milliliter (ng/mL) |
| [14C]-TAK-954 0.5 mg | Cmax: Maximum Observed Plasma Concentration for TAK-954 and TAK-954 Metabolites | THRX-513466 | 0.0143 nanogram per milliliter (ng/mL) |
Primary
Cumulative Percentage of Administered Radioactivity Recovered in Feces
Time frame: Day 1 pre-dose and at multiple time points (up to 264, 312, and 336 hours) post-dose
Population: The PK analysis set included all the participants of safety analysis set with sufficient concentration data to facilitate the derivation of at least 1 PK parameter from the concentration time data. The PK analysis set where data at specified time points was available.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| [14C]-TAK-954 0.5 mg | Cumulative Percentage of Administered Radioactivity Recovered in Feces | 0 to 264 hours | 28.8 percentage of radioactive dose | Standard Deviation 2.5 |
| [14C]-TAK-954 0.5 mg | Cumulative Percentage of Administered Radioactivity Recovered in Feces | 0 to 312 hours | 30.3 percentage of radioactive dose | Standard Deviation 2.5 |
| [14C]-TAK-954 0.5 mg | Cumulative Percentage of Administered Radioactivity Recovered in Feces | 0 to 336 hours | 30.0 percentage of radioactive dose | Standard Deviation 3.5 |
Primary
Cumulative Percentage of Administered Radioactivity Recovered in Urine
Time frame: Day 1 pre-dose and at multiple time points (up to 264, 312, and 336 hours) post-dose
Population: The pharmacokinetic (PK) analysis set included all the participants of safety analysis set with sufficient concentration data to facilitate the derivation of at least 1 PK parameter from the concentration time data. The PK analysis set where data at specified time points was available.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| [14C]-TAK-954 0.5 mg | Cumulative Percentage of Administered Radioactivity Recovered in Urine | 0 to 264 hours | 55.4 percentage of radioactive dose | Standard Deviation 3.2 |
| [14C]-TAK-954 0.5 mg | Cumulative Percentage of Administered Radioactivity Recovered in Urine | 0 to 312 hours | 56.8 percentage of radioactive dose | Standard Deviation 3.2 |
| [14C]-TAK-954 0.5 mg | Cumulative Percentage of Administered Radioactivity Recovered in Urine | 0 to 336 hours | 55.1 percentage of radioactive dose | Standard Deviation 0.4 |
Primary
Cumulative Percentage of Dose Excreted in Feces for TAK-954
The cumulative percentage of dose excreted in feces as TAK-954 derived from 0-168 hour sampling was normalized for 100% recovery.
Time frame: Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose
Population: The PK analysis set included all the participants of safety analysis set with sufficient concentration data to facilitate the derivation of at least 1 PK parameter from the concentration time data. Single sampling method used across participants, therefore there was no measure of dispersion.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| [14C]-TAK-954 0.5 mg | Cumulative Percentage of Dose Excreted in Feces for TAK-954 | 13.7 percentage of dose |
Primary
Cumulative Percentage of Dose Excreted in Urine for TAK-954
Time frame: Day 1 pre-dose and at multiple time points (up to 264, 312, and 336 hours) post-dose
Population: The PK analysis set included all the participants of safety analysis set with sufficient concentration data to facilitate the derivation of at least 1 PK parameter from the concentration time data. The PK analysis set where data at specified time points was available.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| [14C]-TAK-954 0.5 mg | Cumulative Percentage of Dose Excreted in Urine for TAK-954 | 0 to 264 hours | 31.33 percentage of dose | Standard Deviation 3.29 |
| [14C]-TAK-954 0.5 mg | Cumulative Percentage of Dose Excreted in Urine for TAK-954 | 0 to 312 hours | 29.73 percentage of dose | Standard Deviation 4.14 |
| [14C]-TAK-954 0.5 mg | Cumulative Percentage of Dose Excreted in Urine for TAK-954 | 0 to 336 hours | 27.35 percentage of dose | Standard Deviation 0.35 |
Primary
Cumulative Percentage of Radioactivity in Urine and Feces Combined
Time frame: Day 1 pre-dose and at multiple time points (up to 264, 312, and 336 hours) post-dose
Population: The PK analysis set included all the participants of safety analysis set with sufficient concentration data to facilitate the derivation of at least 1 PK parameter from the concentration time data. The PK analysis set where data at specified time points was available.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| [14C]-TAK-954 0.5 mg | Cumulative Percentage of Radioactivity in Urine and Feces Combined | 0 to 264 hours | 84.1 percentage of radioactive dose | Standard Deviation 5.3 |
| [14C]-TAK-954 0.5 mg | Cumulative Percentage of Radioactivity in Urine and Feces Combined | 0 to 312 hours | 87.0 percentage of radioactive dose | Standard Deviation 4.6 |
| [14C]-TAK-954 0.5 mg | Cumulative Percentage of Radioactivity in Urine and Feces Combined | 0 to 336 hours | 85.1 percentage of radioactive dose | Standard Deviation 3.9 |
Primary
Fet Feces: Fraction of Radioactivity Excreted in Feces From Time 0 to Time t for [14C]-TAK-954
Time frame: Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose
Population: The PK analysis set included all the participants of safety analysis set with sufficient concentration data to facilitate the derivation of at least 1 PK parameter from the concentration time data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| [14C]-TAK-954 0.5 mg | Fet Feces: Fraction of Radioactivity Excreted in Feces From Time 0 to Time t for [14C]-TAK-954 | 28.8 percentage of dose | Standard Deviation 2.6 |
Primary
Fet Urine: Fraction of Drug Excreted in Urine From Time 0 to Time t for TAK-954
Time frame: Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose
Population: The PK analysis set included all the participants of safety analysis set with sufficient concentration data to facilitate the derivation of at least 1 PK parameter from the concentration time data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| [14C]-TAK-954 0.5 mg | Fet Urine: Fraction of Drug Excreted in Urine From Time 0 to Time t for TAK-954 | 31.3 percentage of dose | Standard Deviation 3.3 |
Primary
Fet Urine: Fraction of Total Radioactivity Excreted in Urine From Time 0 to Time t for [14C]-TAK-954
Time frame: Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose
Population: The PK analysis set included all the participants of safety analysis set with sufficient concentration data to facilitate the derivation of at least 1 PK parameter from the concentration time data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| [14C]-TAK-954 0.5 mg | Fet Urine: Fraction of Total Radioactivity Excreted in Urine From Time 0 to Time t for [14C]-TAK-954 | 55.6 percentage of dose | Standard Deviation 3.2 |
Primary
Mean Concentration of Total Radioactivity in Whole Blood and Plasma [14C]-TAK-954
Time frame: Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose
Population: The PK analysis set included all the participants of safety analysis set with sufficient concentration data to facilitate the derivation of at least 1 PK parameter from the concentration time data. The PK analysis set where data at specified time points was available.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| [14C]-TAK-954 0.5 mg | Mean Concentration of Total Radioactivity in Whole Blood and Plasma [14C]-TAK-954 | Whole Blood: 0.00 minute | NA nanogram equivalent/milliliter(ng eq/mL) | — |
| [14C]-TAK-954 0.5 mg | Mean Concentration of Total Radioactivity in Whole Blood and Plasma [14C]-TAK-954 | Whole Blood: 0.50 minute | 5.15 nanogram equivalent/milliliter(ng eq/mL) | Standard Deviation 0.908 |
| [14C]-TAK-954 0.5 mg | Mean Concentration of Total Radioactivity in Whole Blood and Plasma [14C]-TAK-954 | Whole Blood: 1 hour | 5.87 nanogram equivalent/milliliter(ng eq/mL) | Standard Deviation 1.26 |
| [14C]-TAK-954 0.5 mg | Mean Concentration of Total Radioactivity in Whole Blood and Plasma [14C]-TAK-954 | Whole Blood: 1.5 hour | 2.88 nanogram equivalent/milliliter(ng eq/mL) | Standard Deviation 0.523 |
| [14C]-TAK-954 0.5 mg | Mean Concentration of Total Radioactivity in Whole Blood and Plasma [14C]-TAK-954 | Whole Blood: 2 hour | 2.40 nanogram equivalent/milliliter(ng eq/mL) | Standard Deviation 0.418 |
| [14C]-TAK-954 0.5 mg | Mean Concentration of Total Radioactivity in Whole Blood and Plasma [14C]-TAK-954 | Whole Blood: 3 hour | 2.05 nanogram equivalent/milliliter(ng eq/mL) | Standard Deviation 0.349 |
| [14C]-TAK-954 0.5 mg | Mean Concentration of Total Radioactivity in Whole Blood and Plasma [14C]-TAK-954 | Whole Blood: 4 hour | 2.09 nanogram equivalent/milliliter(ng eq/mL) | Standard Deviation 0.407 |
| [14C]-TAK-954 0.5 mg | Mean Concentration of Total Radioactivity in Whole Blood and Plasma [14C]-TAK-954 | Whole Blood: 6 hour | 1.79 nanogram equivalent/milliliter(ng eq/mL) | Standard Deviation 0.385 |
| [14C]-TAK-954 0.5 mg | Mean Concentration of Total Radioactivity in Whole Blood and Plasma [14C]-TAK-954 | Whole Blood: 12 hour | 1.40 nanogram equivalent/milliliter(ng eq/mL) | Standard Deviation 0.217 |
| [14C]-TAK-954 0.5 mg | Mean Concentration of Total Radioactivity in Whole Blood and Plasma [14C]-TAK-954 | Whole Blood: 24 hour | 0.923 nanogram equivalent/milliliter(ng eq/mL) | Standard Deviation 0.114 |
| [14C]-TAK-954 0.5 mg | Mean Concentration of Total Radioactivity in Whole Blood and Plasma [14C]-TAK-954 | Whole Blood: 36 hour | 0.583 nanogram equivalent/milliliter(ng eq/mL) | Standard Deviation 0.0874 |
| [14C]-TAK-954 0.5 mg | Mean Concentration of Total Radioactivity in Whole Blood and Plasma [14C]-TAK-954 | Whole Blood: 72 hour | 0.232 nanogram equivalent/milliliter(ng eq/mL) | Standard Deviation 0.053 |
| [14C]-TAK-954 0.5 mg | Mean Concentration of Total Radioactivity in Whole Blood and Plasma [14C]-TAK-954 | Whole Blood: 96 hour | 0.140 nanogram equivalent/milliliter(ng eq/mL) | Standard Deviation 0.042 |
| [14C]-TAK-954 0.5 mg | Mean Concentration of Total Radioactivity in Whole Blood and Plasma [14C]-TAK-954 | Whole Blood: 120 hour | 0.0953 nanogram equivalent/milliliter(ng eq/mL) | Standard Deviation 0.0292 |
| [14C]-TAK-954 0.5 mg | Mean Concentration of Total Radioactivity in Whole Blood and Plasma [14C]-TAK-954 | Whole Blood: 144 hour | 0.0695 nanogram equivalent/milliliter(ng eq/mL) | Standard Deviation 0.0211 |
| [14C]-TAK-954 0.5 mg | Mean Concentration of Total Radioactivity in Whole Blood and Plasma [14C]-TAK-954 | Whole Blood: 168 hour | 0.0449 nanogram equivalent/milliliter(ng eq/mL) | Standard Deviation 0.0363 |
| [14C]-TAK-954 0.5 mg | Mean Concentration of Total Radioactivity in Whole Blood and Plasma [14C]-TAK-954 | Whole Blood: 192 hour | 0.0352 nanogram equivalent/milliliter(ng eq/mL) | Standard Deviation 0.0332 |
| [14C]-TAK-954 0.5 mg | Mean Concentration of Total Radioactivity in Whole Blood and Plasma [14C]-TAK-954 | Whole Blood: 216 hour | 0.0268 nanogram equivalent/milliliter(ng eq/mL) | Standard Deviation 0.0301 |
| [14C]-TAK-954 0.5 mg | Mean Concentration of Total Radioactivity in Whole Blood and Plasma [14C]-TAK-954 | Whole Blood: 240 hour | 0.0246 nanogram equivalent/milliliter(ng eq/mL) | Standard Deviation 0.0273 |
| [14C]-TAK-954 0.5 mg | Mean Concentration of Total Radioactivity in Whole Blood and Plasma [14C]-TAK-954 | Whole Blood: 264 hour | 0.00940 nanogram equivalent/milliliter(ng eq/mL) | Standard Deviation 0.023 |
| [14C]-TAK-954 0.5 mg | Mean Concentration of Total Radioactivity in Whole Blood and Plasma [14C]-TAK-954 | Whole Blood: 288 hour | NA nanogram equivalent/milliliter(ng eq/mL) | — |
| [14C]-TAK-954 0.5 mg | Mean Concentration of Total Radioactivity in Whole Blood and Plasma [14C]-TAK-954 | Whole Blood: 312 hour | NA nanogram equivalent/milliliter(ng eq/mL) | — |
| [14C]-TAK-954 0.5 mg | Mean Concentration of Total Radioactivity in Whole Blood and Plasma [14C]-TAK-954 | Whole Blood: 336 hour | NA nanogram equivalent/milliliter(ng eq/mL) | — |
| [14C]-TAK-954 0.5 mg | Mean Concentration of Total Radioactivity in Whole Blood and Plasma [14C]-TAK-954 | Plasma: 0.00 minute | NA nanogram equivalent/milliliter(ng eq/mL) | — |
| [14C]-TAK-954 0.5 mg | Mean Concentration of Total Radioactivity in Whole Blood and Plasma [14C]-TAK-954 | Plasma: 0.50 minute | 5.74 nanogram equivalent/milliliter(ng eq/mL) | Standard Deviation 1.72 |
| [14C]-TAK-954 0.5 mg | Mean Concentration of Total Radioactivity in Whole Blood and Plasma [14C]-TAK-954 | Plasma: 1 hour | 6.29 nanogram equivalent/milliliter(ng eq/mL) | Standard Deviation 1.22 |
| [14C]-TAK-954 0.5 mg | Mean Concentration of Total Radioactivity in Whole Blood and Plasma [14C]-TAK-954 | Plasma: 1.5 hour | 3.06 nanogram equivalent/milliliter(ng eq/mL) | Standard Deviation 0.528 |
| [14C]-TAK-954 0.5 mg | Mean Concentration of Total Radioactivity in Whole Blood and Plasma [14C]-TAK-954 | Plasma: 2 hour | 2.59 nanogram equivalent/milliliter(ng eq/mL) | Standard Deviation 0.566 |
| [14C]-TAK-954 0.5 mg | Mean Concentration of Total Radioactivity in Whole Blood and Plasma [14C]-TAK-954 | Plasma: 3 hour | 2.27 nanogram equivalent/milliliter(ng eq/mL) | Standard Deviation 0.495 |
| [14C]-TAK-954 0.5 mg | Mean Concentration of Total Radioactivity in Whole Blood and Plasma [14C]-TAK-954 | Plasma: 4 hour | 2.17 nanogram equivalent/milliliter(ng eq/mL) | Standard Deviation 0.437 |
| [14C]-TAK-954 0.5 mg | Mean Concentration of Total Radioactivity in Whole Blood and Plasma [14C]-TAK-954 | Plasma: 6 hour | 1.77 nanogram equivalent/milliliter(ng eq/mL) | Standard Deviation 0.433 |
| [14C]-TAK-954 0.5 mg | Mean Concentration of Total Radioactivity in Whole Blood and Plasma [14C]-TAK-954 | Plasma: 12 hour | 1.34 nanogram equivalent/milliliter(ng eq/mL) | Standard Deviation 0.209 |
| [14C]-TAK-954 0.5 mg | Mean Concentration of Total Radioactivity in Whole Blood and Plasma [14C]-TAK-954 | Plasma: 24 hour | 0.983 nanogram equivalent/milliliter(ng eq/mL) | Standard Deviation 0.104 |
| [14C]-TAK-954 0.5 mg | Mean Concentration of Total Radioactivity in Whole Blood and Plasma [14C]-TAK-954 | Plasma: 36 hour | 0.601 nanogram equivalent/milliliter(ng eq/mL) | Standard Deviation 0.0567 |
| [14C]-TAK-954 0.5 mg | Mean Concentration of Total Radioactivity in Whole Blood and Plasma [14C]-TAK-954 | Plasma: 48 hour | 0.443 nanogram equivalent/milliliter(ng eq/mL) | Standard Deviation 0.0478 |
| [14C]-TAK-954 0.5 mg | Mean Concentration of Total Radioactivity in Whole Blood and Plasma [14C]-TAK-954 | Plasma: 72 hour | 0.271 nanogram equivalent/milliliter(ng eq/mL) | Standard Deviation 0.0502 |
| [14C]-TAK-954 0.5 mg | Mean Concentration of Total Radioactivity in Whole Blood and Plasma [14C]-TAK-954 | Plasma: 96 hour | 0.169 nanogram equivalent/milliliter(ng eq/mL) | Standard Deviation 0.0368 |
| [14C]-TAK-954 0.5 mg | Mean Concentration of Total Radioactivity in Whole Blood and Plasma [14C]-TAK-954 | Plasma: 120 hour | 0.123 nanogram equivalent/milliliter(ng eq/mL) | Standard Deviation 0.0378 |
| [14C]-TAK-954 0.5 mg | Mean Concentration of Total Radioactivity in Whole Blood and Plasma [14C]-TAK-954 | Plasma: 144 hour | 0.0907 nanogram equivalent/milliliter(ng eq/mL) | Standard Deviation 0.0276 |
| [14C]-TAK-954 0.5 mg | Mean Concentration of Total Radioactivity in Whole Blood and Plasma [14C]-TAK-954 | Plasma: 168 hour | 0.0689 nanogram equivalent/milliliter(ng eq/mL) | Standard Deviation 0.0264 |
| [14C]-TAK-954 0.5 mg | Mean Concentration of Total Radioactivity in Whole Blood and Plasma [14C]-TAK-954 | Plasma: 192 hour | 0.0552 nanogram equivalent/milliliter(ng eq/mL) | Standard Deviation 0.0163 |
| [14C]-TAK-954 0.5 mg | Mean Concentration of Total Radioactivity in Whole Blood and Plasma [14C]-TAK-954 | Plasma: 216 hour | 0.0480 nanogram equivalent/milliliter(ng eq/mL) | Standard Deviation 0.0131 |
| [14C]-TAK-954 0.5 mg | Mean Concentration of Total Radioactivity in Whole Blood and Plasma [14C]-TAK-954 | Plasma: 240 hour | 0.0486 nanogram equivalent/milliliter(ng eq/mL) | Standard Deviation 0.0175 |
| [14C]-TAK-954 0.5 mg | Mean Concentration of Total Radioactivity in Whole Blood and Plasma [14C]-TAK-954 | Plasma: 264 hour | 0.0407 nanogram equivalent/milliliter(ng eq/mL) | Standard Deviation 0.0114 |
| [14C]-TAK-954 0.5 mg | Mean Concentration of Total Radioactivity in Whole Blood and Plasma [14C]-TAK-954 | Plasma: 288 hour | 0.0429 nanogram equivalent/milliliter(ng eq/mL) | Standard Deviation 0.0166 |
| [14C]-TAK-954 0.5 mg | Mean Concentration of Total Radioactivity in Whole Blood and Plasma [14C]-TAK-954 | Plasma: 312 hour | 0.0413 nanogram equivalent/milliliter(ng eq/mL) | Standard Deviation 0.00559 |
| [14C]-TAK-954 0.5 mg | Mean Concentration of Total Radioactivity in Whole Blood and Plasma [14C]-TAK-954 | Plasma: 336 hour | 0.0349 nanogram equivalent/milliliter(ng eq/mL) | Standard Deviation 0.007 |
Primary
Mean Percent of Total Radioactivity in Plasma for TAK-954 and TAK-954 Metabolites
Time frame: Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose
Population: The PK analysis set included all the participants of safety analysis set with sufficient concentration data to facilitate the derivation of at least 1 PK parameter from the concentration time data. Data is reported for TAK-954. Data for metabolites are not reported because none exceeded greater than (\>) 6% of the total plasma radioactivity.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| [14C]-TAK-954 0.5 mg | Mean Percent of Total Radioactivity in Plasma for TAK-954 and TAK-954 Metabolites | 74.28 percentage of total radioactivity | Standard Deviation 8.18 |
Primary
Normalized Recovery as Percentage of Dose for TAK-954 and TAK-954 Metabolites in Feces
Percentage of dose recovered for TAK-954 and its metabolites derived from 0-168 hour sampling was normalized for 100% recovery.
Time frame: Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose
Population: PK analysis set: All participants of safety set with sufficient data to facilitate at least 1 PK parameter from concentration time data. Single value is available for Metabolite (M) 16, M4, and M5 because they co-eluted under chromatographic conditions. Single sampling method used across participants, therefore there was no measure of dispersion.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| [14C]-TAK-954 0.5 mg | Normalized Recovery as Percentage of Dose for TAK-954 and TAK-954 Metabolites in Feces | M3 | 8.8 percentage of dose |
| [14C]-TAK-954 0.5 mg | Normalized Recovery as Percentage of Dose for TAK-954 and TAK-954 Metabolites in Feces | M5, M4, and M16 | 3.4 percentage of dose |
| [14C]-TAK-954 0.5 mg | Normalized Recovery as Percentage of Dose for TAK-954 and TAK-954 Metabolites in Feces | M17 | 0.8 percentage of dose |
| [14C]-TAK-954 0.5 mg | Normalized Recovery as Percentage of Dose for TAK-954 and TAK-954 Metabolites in Feces | M7 | 0.5 percentage of dose |
| [14C]-TAK-954 0.5 mg | Normalized Recovery as Percentage of Dose for TAK-954 and TAK-954 Metabolites in Feces | M10 | 0.5 percentage of dose |
| [14C]-TAK-954 0.5 mg | Normalized Recovery as Percentage of Dose for TAK-954 and TAK-954 Metabolites in Feces | TAK-954 | 13.7 percentage of dose |
Primary
Normalized Recovery as Percentage of Dose for TAK-954 and TAK-954 Metabolites in Urine
Percentage of dose recovered for TAK-954 and its metabolites derived from 0-168 hour sampling was normalized for 100% recovery.
Time frame: Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose
Population: PK analysis set: All participants of safety set with sufficient data to facilitate at least 1 PK parameter from concentration time data. Single value is available for Metabolite (M) 16, M4, and M5 because they co-eluted under chromatographic conditions. Single sampling method used across participants, therefore there was no measure of dispersion.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| [14C]-TAK-954 0.5 mg | Normalized Recovery as Percentage of Dose for TAK-954 and TAK-954 Metabolites in Urine | M1 | 3.0 Percentage of dose |
| [14C]-TAK-954 0.5 mg | Normalized Recovery as Percentage of Dose for TAK-954 and TAK-954 Metabolites in Urine | M3 | 4.8 Percentage of dose |
| [14C]-TAK-954 0.5 mg | Normalized Recovery as Percentage of Dose for TAK-954 and TAK-954 Metabolites in Urine | M14 | 4.3 Percentage of dose |
| [14C]-TAK-954 0.5 mg | Normalized Recovery as Percentage of Dose for TAK-954 and TAK-954 Metabolites in Urine | M5, M4, and M16 | 1.6 Percentage of dose |
| [14C]-TAK-954 0.5 mg | Normalized Recovery as Percentage of Dose for TAK-954 and TAK-954 Metabolites in Urine | M17 | 0.8 Percentage of dose |
| [14C]-TAK-954 0.5 mg | Normalized Recovery as Percentage of Dose for TAK-954 and TAK-954 Metabolites in Urine | M9 | 0.6 Percentage of dose |
| [14C]-TAK-954 0.5 mg | Normalized Recovery as Percentage of Dose for TAK-954 and TAK-954 Metabolites in Urine | M10 | 0.5 Percentage of dose |
| [14C]-TAK-954 0.5 mg | Normalized Recovery as Percentage of Dose for TAK-954 and TAK-954 Metabolites in Urine | TAK-954 | 44.3 Percentage of dose |
Primary
Normalized Recovery as Percentage of Dose for TAK-954 and TAK-954 Metabolites in Urine and Feces Combined
Percentage of dose recovered for TAK-954 and its metabolites derived from 0-168 hour sampling was normalized for 100% recovery.
Time frame: Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose
Population: PK analysis set: All participants of safety set with sufficient data to facilitate at least 1 PK parameter from concentration time data. Single value is available for Metabolite (M) 16, M4, and M5 because they co-eluted under chromatographic conditions. Single sampling method used across participants, therefore there was no measure of dispersion.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| [14C]-TAK-954 0.5 mg | Normalized Recovery as Percentage of Dose for TAK-954 and TAK-954 Metabolites in Urine and Feces Combined | M1 | 3.0 percentage of dose |
| [14C]-TAK-954 0.5 mg | Normalized Recovery as Percentage of Dose for TAK-954 and TAK-954 Metabolites in Urine and Feces Combined | M3 | 13.6 percentage of dose |
| [14C]-TAK-954 0.5 mg | Normalized Recovery as Percentage of Dose for TAK-954 and TAK-954 Metabolites in Urine and Feces Combined | M14 | 4.3 percentage of dose |
| [14C]-TAK-954 0.5 mg | Normalized Recovery as Percentage of Dose for TAK-954 and TAK-954 Metabolites in Urine and Feces Combined | M4, M5, and M16 | 5.0 percentage of dose |
| [14C]-TAK-954 0.5 mg | Normalized Recovery as Percentage of Dose for TAK-954 and TAK-954 Metabolites in Urine and Feces Combined | M17 | 1.6 percentage of dose |
| [14C]-TAK-954 0.5 mg | Normalized Recovery as Percentage of Dose for TAK-954 and TAK-954 Metabolites in Urine and Feces Combined | M7 | 0.5 percentage of dose |
| [14C]-TAK-954 0.5 mg | Normalized Recovery as Percentage of Dose for TAK-954 and TAK-954 Metabolites in Urine and Feces Combined | M9 | 0.6 percentage of dose |
| [14C]-TAK-954 0.5 mg | Normalized Recovery as Percentage of Dose for TAK-954 and TAK-954 Metabolites in Urine and Feces Combined | M10 | 1.0 percentage of dose |
| [14C]-TAK-954 0.5 mg | Normalized Recovery as Percentage of Dose for TAK-954 and TAK-954 Metabolites in Urine and Feces Combined | TAK-954 | 58.0 percentage of dose |
Primary
t1/2z: Terminal Disposition Phase Half-life in Plasma for TAK-954 and TAK-954 Metabolites
Time frame: Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose
Population: The PK analysis set. PK data for metabolites could not be evaluated since metabolites were \< lower limit of quantification and apparent terminal elimination portion of the concentration-time curve could not be characterized.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| [14C]-TAK-954 0.5 mg | t1/2z: Terminal Disposition Phase Half-life in Plasma for TAK-954 and TAK-954 Metabolites | 34.3 hour |
Primary
t1/2z: Terminal Disposition Phase Half-life of Radioactivity in Plasma and Whole Blood for [14C]-TAK-954
Time frame: Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose
Population: The PK analysis set included all the participants of safety analysis set with sufficient concentration data to facilitate the derivation of at least 1 PK parameter from the concentration time data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| [14C]-TAK-954 0.5 mg | t1/2z: Terminal Disposition Phase Half-life of Radioactivity in Plasma and Whole Blood for [14C]-TAK-954 | Plasma | 70.0 hour |
| [14C]-TAK-954 0.5 mg | t1/2z: Terminal Disposition Phase Half-life of Radioactivity in Plasma and Whole Blood for [14C]-TAK-954 | Whole Blood | 46.4 hour |
Primary
Tmax: Time to Reach the Maximum Plasma and Whole Blood Radioactivity for [14C]-TAK-954
Time frame: Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose
Population: The PK analysis set included all the participants of safety analysis set with sufficient concentration data to facilitate the derivation of at least 1 PK parameter from the concentration time data.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| [14C]-TAK-954 0.5 mg | Tmax: Time to Reach the Maximum Plasma and Whole Blood Radioactivity for [14C]-TAK-954 | Plasma | 1.00 hour |
| [14C]-TAK-954 0.5 mg | Tmax: Time to Reach the Maximum Plasma and Whole Blood Radioactivity for [14C]-TAK-954 | Whole Blood | 1.00 hour |
Primary
Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-954 and TAK-954 Metabolites
Time frame: Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose
Population: The PK analysis set included all the participants of safety analysis set with sufficient concentration data to facilitate the derivation of at least 1 PK parameter from the concentration time data. PK data for TAK-954 metabolite (THRX913682) could not be evaluated since metabolites were \< lower limit of quantification.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| [14C]-TAK-954 0.5 mg | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-954 and TAK-954 Metabolites | TAK-954 | 1.00 hour |
| [14C]-TAK-954 0.5 mg | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-954 and TAK-954 Metabolites | THRX-513466 | 1.00 hour |
Primary
Vz: Volume of Distribution During the Terminal Disposition Phase After Intravenous Administration for [14C]-TAK-954
Time frame: Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose
Population: No participant was analyzed since this outcome measure was not planned to be assessed but added in the protocol summary by error.
Primary
Vz: Volume of Distribution During the Terminal Disposition Phase After Intravenous Administration for TAK-954
Time frame: Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose
Population: The PK analysis set included all the participants of safety analysis set with sufficient concentration data to facilitate the derivation of at least 1 PK parameter from the concentration time data.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| [14C]-TAK-954 0.5 mg | Vz: Volume of Distribution During the Terminal Disposition Phase After Intravenous Administration for TAK-954 | 444 liter |
Secondary
Percentage of Participants Who Experience at Least One Treatment-emergent Adverse Event (TEAE)
Time frame: Baseline up to Day 31
Population: The safety analysis set included all participants who were enrolled in the study and received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| [14C]-TAK-954 0.5 mg | Percentage of Participants Who Experience at Least One Treatment-emergent Adverse Event (TEAE) | 50.0 percentage of participants |
Secondary
Percentage of Participants With Adverse Events (AEs) Leading to Discontinuation of [14C]-TAK-954
Time frame: Baseline up to Day 15
Population: The safety analysis set included all participants who were enrolled in the study and received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| [14C]-TAK-954 0.5 mg | Percentage of Participants With Adverse Events (AEs) Leading to Discontinuation of [14C]-TAK-954 | 0.0 percentage of participants |
Secondary
Ratio of AUC∞: Ratio of Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-954 to Total Radioactivity in Plasma TAK-954
Time frame: Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose
Population: The PK analysis set included all the participants of safety analysis set with sufficient concentration data to facilitate the derivation of at least 1 PK parameter from the concentration time data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| [14C]-TAK-954 0.5 mg | Ratio of AUC∞: Ratio of Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-954 to Total Radioactivity in Plasma TAK-954 | 0.642 ratio | Standard Deviation 0.0741 |
Secondary
Ratio of Total Radioactivity in Whole Blood to Plasma
Time frame: Day 1 pre-dose and at multiple time points (up to 264 hours) post-dose
Population: The PK analysis set included all the participants of safety analysis set with sufficient concentration data to facilitate the derivation of at least 1 PK parameter from the concentration time data. The PK analysis set where data at specified time points was available.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| [14C]-TAK-954 0.5 mg | Ratio of Total Radioactivity in Whole Blood to Plasma | 0.50 minute | 0.92 ratio | Standard Deviation 0.13 |
| [14C]-TAK-954 0.5 mg | Ratio of Total Radioactivity in Whole Blood to Plasma | 1 hour | 0.93 ratio | Standard Deviation 0.06 |
| [14C]-TAK-954 0.5 mg | Ratio of Total Radioactivity in Whole Blood to Plasma | 1.5 hour | 0.94 ratio | Standard Deviation 0.09 |
| [14C]-TAK-954 0.5 mg | Ratio of Total Radioactivity in Whole Blood to Plasma | 2 hour | 0.94 ratio | Standard Deviation 0.15 |
| [14C]-TAK-954 0.5 mg | Ratio of Total Radioactivity in Whole Blood to Plasma | 3 hour | 0.92 ratio | Standard Deviation 0.17 |
| [14C]-TAK-954 0.5 mg | Ratio of Total Radioactivity in Whole Blood to Plasma | 4 hour | 0.96 ratio | Standard Deviation 0.06 |
| [14C]-TAK-954 0.5 mg | Ratio of Total Radioactivity in Whole Blood to Plasma | 6 hour | 1.02 ratio | Standard Deviation 0.14 |
| [14C]-TAK-954 0.5 mg | Ratio of Total Radioactivity in Whole Blood to Plasma | 12 hour | 1.04 ratio | Standard Deviation 0.04 |
| [14C]-TAK-954 0.5 mg | Ratio of Total Radioactivity in Whole Blood to Plasma | 24 hour | 0.94 ratio | Standard Deviation 0.07 |
| [14C]-TAK-954 0.5 mg | Ratio of Total Radioactivity in Whole Blood to Plasma | 36 hour | 0.97 ratio | Standard Deviation 0.11 |
| [14C]-TAK-954 0.5 mg | Ratio of Total Radioactivity in Whole Blood to Plasma | 72 hour | 0.86 ratio | Standard Deviation 0.08 |
| [14C]-TAK-954 0.5 mg | Ratio of Total Radioactivity in Whole Blood to Plasma | 96 hour | 0.82 ratio | Standard Deviation 0.13 |
| [14C]-TAK-954 0.5 mg | Ratio of Total Radioactivity in Whole Blood to Plasma | 120 hour | 0.78 ratio | Standard Deviation 0.12 |
| [14C]-TAK-954 0.5 mg | Ratio of Total Radioactivity in Whole Blood to Plasma | 144 hour | 0.79 ratio | Standard Deviation 0.21 |
| [14C]-TAK-954 0.5 mg | Ratio of Total Radioactivity in Whole Blood to Plasma | 168 hour | 0.85 ratio | Standard Deviation 0.16 |
| [14C]-TAK-954 0.5 mg | Ratio of Total Radioactivity in Whole Blood to Plasma | 192 hour | 1.17 ratio | Standard Deviation 0.65 |
| [14C]-TAK-954 0.5 mg | Ratio of Total Radioactivity in Whole Blood to Plasma | 216 hour | 1.06 ratio | Standard Deviation 0.37 |
| [14C]-TAK-954 0.5 mg | Ratio of Total Radioactivity in Whole Blood to Plasma | 240 hour | 1.04 ratio | Standard Deviation 0.35 |
| [14C]-TAK-954 0.5 mg | Ratio of Total Radioactivity in Whole Blood to Plasma | 264 hour | 0.97 ratio | — |